| 1. |
- Lindstrom, Sofie, et al.
(author)
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Intense and widespread seismicity during the end-Triassic mass extinction due to emplacement of a large igneous province
- 2015
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In: Geology. - 0091-7613. ; 43:5, s. 387-390
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Journal article (peer-reviewed)abstract
- Multiple levels of earthquake-induced soft-sediment deformations (seismites) are concentrated in the end-Triassic mass extinction interval across Europe. The repetitive nature of the seismites rules out an origin by an extraterrestrial impact. Instead, this intense seismic activity is linked to the formation of the Central Atlantic magmatic province (CAMP). By the earliest Jurassic the seismic activity had ceased, while extrusive volcanism still continued and biotic recovery was on its way. This suggests that magmatic intrusions into sedimentary strata during early stages of CAMP formation caused emission of gases (SO2, halocarbons, polycyclic aromatic hydrocarbons) that may have played a major part in the biotic crisis.
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| 2. |
- Gedebjerg, Anne, et al.
(author)
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CRP, C-Peptide, and Risk of First-Time Cardiovascular Events and Mortality in Early Type 2 Diabetes : A Danish Cohort Study
- 2023
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 46:5, s. 1037-1045
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Journal article (peer-reviewed)abstract
- We investigated the relationship between hs-CRP, a marker of low-grade inflam-mation, alone or in combination with C-peptide, a marker of hyperinsulinemia/ insulin resistance, and risk for cardiovascular events (CVEs) and mortality in patients recently diagnosed with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS In patients with recent-onset T2D, we measured serum hs-CRP (n = 7,301) and C-peptide (n = 5,765) in the prospective Danish Centre for Strategic Research in Type 2 Diabetes cohort study. Patients with no prior CVE (n = 6,407) were followed until first myocardial infarction, stroke, coronary revascularization, or cardiovascular death, and all patients (n = 7,301) were followed for all-cause mortality. We com-puted adjusted hazard ratios (aHRs) by Cox regression and tested for the interaction between hs-CRP and C-peptide. RESULTS During follow-up (median 4.8 years), high (>3 mg/L) versus low (<1 mg/L) hs-CRP was associated with increased CVE risk (aHR 1.45 [95% CI 1.07–1.96]) and with even greater risk of all-cause mortality (2.47 [1.88–3.25]). Compared with patients with low hs-CRP (£3 mg/L) and low C-peptide (<1,470 pmol/L), those with high lev-els of both biomarkers had the highest CVE (1.61 [1.10–2.34]) and all-cause mortality risk (2.36 [1.73–3.21]). Among patients with high C-peptide, risk of CVEs did not differ by low or high hs-CRP, whereas risk of all-cause mortality did. CONCLUSIONS The finding of high hs-CRP as a stronger prognostic biomarker of all-cause mortality than of CVEs may facilitate improved early detection and prevention of deadly diseases besides CVEs. Conversely, elevated C-peptide as a strong CVE biomarker sup-ports the need to target hyperinsulinemia/insulin resistance in T2D CVE prevention.
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| 3. |
- Hønge, Bo L., et al.
(author)
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T-cell and B-cell perturbations are similar in ART-naive HIV-1 and HIV-1/2 dually infected patients
- 2019
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In: AIDS. - 0269-9370. ; 33:7, s. 1143-1153
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Journal article (peer-reviewed)abstract
- BACKGROUND: HIV-2 may slow progression of a subsequently acquired HIV-1 infection through cross-neutralizing antibodies and polyfunctional CD8 T cells. We hypothesized that HIV-1/2 dually infected patients compared with HIV-1-infected patients had more preserved immune maturation subsets and less immune activation of T and B cells. METHODS: ART-naive patients with HIV-1 (n = 83) or HIV-1/2 dual (n = 27) infections were included in this cross-sectional study at an HIV clinic in Guinea-Bissau. Peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry according to T-cell maturation and activation, regulatory T-cell fraction, and B-cell maturation and activation. RESULTS: HIV-1/2 dually infected patients had lower levels of HIV-1 RNA compared with patients with HIV-1 infection, but the levels of total HIV RNA (HIV-1 and HIV-2) were similar in the two patient groups. T-cell maturation, and proportions of regulatory T cells (FoxP3+) were also similar in the two groups. HIV-1/2 dually infected patients had higher proportions of CD4 and CD8 T cells positive for the activation marker CD38, but there was no difference in other T-cell activation markers (CD28, CTLA-4, PD-1). HIV-1/2 dually infected patients also had higher proportions of IgM-only B cells and plasmablasts. CONCLUSION: HIV-1/2 was not associated with less immune perturbations than for HIV-1 infection.
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| 4. |
- Jespersen, Sanne, et al.
(author)
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Protease Inhibitors or NNRTIs as First-Line HIV-1 Treatment in West Africa (PIONA) : A Randomized Controlled Trial
- 2018
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In: JAIDS. - 1944-7884. ; 79:3, s. 386-393
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Journal article (peer-reviewed)abstract
- BACKGROUND: Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are recommended as part of first-line treatment for HIV-1 in Africa. However, NNRTI-based regimens are more prone to resistance development than protease inhibitors (PIs) in a context in which drug interruptions are frequent. The aim of this study was to compare the efficacy and tolerability of NNRTIs with PIs in HIV-1-infected patients in Guinea-Bissau.METHODS: This open-label randomized, 2-arm superiority trial compared the use of 2 NRTIs plus either one NNRTI (efavirenz or nevirapine) or one PI (lopinavir/ritonavir) in treatment-naive HIV-1-infected adults in the Bissau HIV Cohort (ClinicalTrials.gov, NCT0019235). The primary endpoint was HIV-1 RNA <400 copies per milliliter after 12 months of treatment.RESULTS: Between May 5, 2011, and April 26, 2013, 400 patients were included in the study. In an intention-to-treat analysis, the proportions of patients with viral suppression were similar in the NNRTI [65/197 (33.0%)] and PI [68/203 (33.5%)] arms (P = 0.92). No PI resistance was detected, but high-level NNRTI resistance was seen in 17/30 (56.7%) of NNRTI vs. 3/26 (11.5%) of PI-treated patients, P < 0.01. After 1 year of follow-up, 65 patients died (16.3%) and 93 were lost to follow-up (23.3%). There was no difference in mortality (hazard ratio 0.84, 95% confidence interval: 0.51 to 1.36) or frequency of clinical adverse events between treatment arms [NNRTI: 73/197 (37.1%); and PI: 69/203 (34.0%); P = 0.52].CONCLUSIONS: In patients at an HIV clinic in Guinea-Bissau, treatment with PIs led to less development of resistance compared with NNRTIs but was not superior in terms of viral suppression, CD4 cell increment, mortality, or severe adverse events.
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| 5. |
- Krarup, Anne L., et al.
(author)
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The Short Health Scale A Simple, Valid, Reliable, and Responsive Way of Measuring Subjective Health in Patients With Irritable Bowel Syndrome
- 2015
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In: Journal of Clinical Gastroenterology. - : Lippincott, Williams andamp; Wilkins: No Hybrid Open Access. - 0192-0790 .- 1539-2031. ; 49:7, s. 565-570
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Journal article (peer-reviewed)abstract
- Goals:To evaluate validity, reliability, and responsiveness of the Short Health Scale (SHS) in irritable bowel syndrome (IBS) patients.Background:Subjective health assessment is central when treating patients with IBS. The Short Health Scale is a quick 4-item questionnaire covering most aspects of subjective health that has been validated for inflammatory bowel disease.Study:To test validity, 451 patients with IBS (mean age, 38 y; 81% females) completed the SHS and questionnaires assessing IBS symptom severity (IBS-SSS), gastrointestinal (GI)-specific anxiety (VSI), and quality of life (IBSQOL). To evaluate reliability and responsiveness to changes, the questionnaires were repeated after 2 weeks in 18 patients, and after 12 weeks in 212 patients who had completed a patient-education program.Results:Validity was documented with (1) gradually increasing mean scores for all 4 SHS items with increasing IBS-SSS (Pless than0.0001), and (2) correlations between the 4 SHS items and the corresponding items from the other subjective health assessment tools [item 1 (symptom burden): =0.67, item 2 (daily function): =-0.44 to -0.46, item 3 (disease-related worry): =-0.51 to 0.57, item 4 (general well-being): =-0.34 to -0.46, Pless than0.0001]. Reliability was confirmed (Spearman greater than0.7 and intraclass correlations greater than0.7). Responsiveness was good with responders to the patient-education program (IBS-SSS reduction 50 points) having significant reductions in 3 of the SHS items (Pless than0.05), and borderline change for the fourth SHS item (P=0.06).Conclusions:SHS is a health measure that shows promising evidence of validity, reliability, and responsiveness in IBS patients. It is quickly completed and evaluated, which supports its usefulness in the busy clinical practice.
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| 6. |
- Krarup, Niels Henrik, et al.
(author)
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Quality of cardiopulmonary resuscitation in out-of-hospital cardiac arrest is hampered by interruptions in chest compressions-A nationwide prospective feasibility study
- 2011
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In: Resuscitation. - : Elsevier BV. - 1873-1570 .- 0300-9572. ; 82:3, s. 263-269
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Journal article (peer-reviewed)abstract
- Aim of the study: Quality of cardiopulmonary resuscitation (CPR) is a critical determinant of outcome following out-of-hospital cardiac arrest. The aim of our study was to evaluate the quality of CPR provided by emergency medical service providers (Basic Life Support (BLS) capability) and emergency medical service providers assisted by paramedics, nurse anesthetists or physician-manned ambulances (Advanced Life Support (ALS) capability) in a nationwide, unselected cohort of out-of-hospital cardiac arrest cases. Methods: We conducted a prospective, observational study of out-of-hospital cardiac arrest with non-traumatic etiology (>18 years of age) occurring from the 1st to the 31st of January 2009 and treated by the primary Danish emergency medical service operator, covering approximately 85% of the population. One hundred and ninety-one cases were eligible for analysis. Follow-up was up to one year or death. Quality of CPR was evaluated using measurements of transthoracic impedance. Results: The majority of patients were treated by ambulances with ALS capability (54%). Interruptions in CPR related to loading of the patient into the emergency medical service vehicle were substantial, but independent of whether patients were managed by ALS or BLS capable units (222s versus 224s, P=0.76) as were duration of interruptions during rhythm analysis alone (20s versus 22s, P=0.33) and defibrillation (24s versus 26s, P=0.07). Conclusions: Nationwide, routine monitoring of transthoracic impedance is feasible. CPR is hampered by extended interruptions, particularly during loading of the patient into the emergency medical service vehicle, rhythm analysis and defibrillation. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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| 7. |
- Rich, Rebecca L., et al.
(author)
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A global benchmark study using affinity-based biosensors
- 2009
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In: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 386:2, s. 194-216
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Journal article (peer-reviewed)abstract
- To explore the variability in biosensor studies, 150 participants from 20 countries were given the same protein samples and asked to determine kinetic rate constants for the interaction. We chose a protein system that was amenable to analysis using different biosensor platforms as well as by users of different expertise levels. The two proteins (a 50-kDa Fab and a 60-kDa glutathione S-transferase [GST] antigen) form a relatively high-affinity complex, so participants needed to optimize several experimental parameters, including ligand immobilization and regeneration conditions as well as analyte concentrations and injection/dissociation times. Although most participants collected binding responses that could be fit to yield kinetic parameters, the quality of a few data sets could have been improved by optimizing the assay design. Once these outliers were removed, the average reported affinity across the remaining panel of participants was 620 pM with a standard deviation of 980 pM. These results demonstrate that when this biosensor assay was designed and executed appropriately, the reported rate constants were consistent, and independent of which protein was immobilized and which biosensor was used.
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| 8. |
- Ronnow, Carl Fredrik, et al.
(author)
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Lymphovascular Infiltration, Not Depth of Invasion, is the Critical Risk Factor of Metastases in Early Colorectal Cancer : Retrospective Population-based Cohort Study on Prospectively Collected Data, including Validation
- 2022
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In: Annals of Surgery. - 0003-4932. ; 275:1, s. 148-154
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Journal article (peer-reviewed)abstract
- Objective: To identify clinical and histopathological risk factors of LNM in T1 CRC. Summary of Background Data: The requisite of additional surgery after locally resected T1 CRC is dependent on the risk of LNM. Depth of submucosal invasion is used as a key predictor of lymphatic metastases although data are conflicting on its actual impact. Methods: Retrospective population-based cohort study on prospectively collected data on all patients with T1 CRC undergoing surgical resection in Sweden, 2009-2017 and Denmark 2016-2018. The Danish cohort was used for validation. Potential risk factors of LNM investigated were; age, sex, tumor location, submucosal invasion, grade of differentiation, mucinous subtype, lymphovascular, and perineural invasion. Results: One hundred fifty out of the 1439 included patients (10%) had LNM. LVI (P < 0.001), perineural invasion (P < 0.001), mucinous subtype (P = 0.006), and age <60 years (P < 0.001) were identified as independent risk factors whereas deep submucosal invasion was only a dependent (P = 0.025) risk factor and not significant in multivariate analysis (P = 0.075). The incidence ofLNMwas 51/882 (6%) in absence of the independent risk factors. The Danish validation cohort, confirmed our findings regarding the role of submucosal invasion, LVI, and age. Conclusions: This is a large study on LNM in T1 CRC, including validation, showing that LVI and perineural invasion, mucinous subtype, and low age constitute independent risk factors, whereas depth of submucosal invasion is not an independent risk factor of LNM. Thus, our findings provide a useful basis for management of patients after local excision of early CRC.
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